Journal Article

Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases

Zhaohui Wang, Jun Zhang, Yuan Wang, Rui Xing, Chongqin Yi, Huishan Zhu, Xianwei Chen, Jiao Guo, Weixin Guo, Wenmei Li, Lin Wu, Youyong Lu and Siqi Liu

in Carcinogenesis

Volume 34, issue 1, pages 128-138
Published in print January 2013 | ISSN: 0143-3334
Published online September 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs295
Matrine, a novel autophagy inhibitor, blocks trafficking and the proteolytic activation of lysosomal proteases

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Autophagy has been referred to as a double-edged sword in tumorigenesis and tumor progression. Emerging evidence suggests that pharmacological modulation of autophagy is a promising therapeutic strategy for cancer. However, few autophagy-modulating compounds are currently approved for clinical use in humans. Matrine is a natural compound extracted from traditional Chinese medicine that is widely used for treatment of a variety of diseases without any obvious side effects. Recently, matrine has been reported to induce autophagy and autophagic cell death in cancer cells, although the underlying mechanisms have yet to be elucidated. Here, we systematically examined the autophagic events induced by matrine in SGC7901 cells. The accumulation of autophagic vacuoles in matrine-treated cells was verified by the conversion of microtubule-associated protein light chain 3 as well as confocal and transmission electron microscopy. Furthermore, we demonstrated that matrine blocked autophagic degradation by impairing the activities of lysosomal proteases. Moreover, confocal microscopy and gradient ultracentrifugation revealed that the trafficking processes and proteolytic activation of cathepsins were inhibited by matrine. Using a pH sensor probe, we found elevated pH values in endosomes/lysosomes in response to matrine treatment. Therefore, matrine seems to be a novel autophagy inhibitor that can modulate the maturation process of lysosomal proteases.

Journal Article.  7234 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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